The present invention relates to a new and improved process for producing cephalosporin derivatives in high yield utilizing a novel acylating agent, the 3-position of which being substituted by acetoxymethyl or tetrazolylthiomethyl and the 7-acyl group of which being substituted by D-mandelic acid derivatives, which is represented by the following formula (I); ##STR4## wherein X is ##STR5## R.sup.1 is hydrogen or --CHO.
The process for the preparation of the compound of formula (I), according to the present invention comprises reacting carboxylic acid of the following formula (III) with the compound of the following formula (IV) in the presence of a novel acylating agent having the following formula(II). ##STR6## wherein, R.sup.2 is methyl, ethyl, propyl, phenyl, and R.sup.1 and X are the same as defined above.
The compound of formula (I) wherein X is substituted by 1-methyl-5-mercaptoteitraxole is known as an antibiotic substance, which is stable for liver enzyme as well as for cephalosporinase which is proliferated by gram-negative bacterium.
Various processes for preparing the compound of formula (I) are known in the art as examplified by Korean Patent Publication No. 75-299, U.S. Pat. Nos. 3,641,021, 3,928,592, 3,928,337, and 4,006,138 and Japanese Kokai No. 52-83,956.
Acylation processes described in the above prior art processes may be classified into two typical groups. In one process, the compound of formula (I) is produced by reacting an acid chloride which is prepared from the compound of formula (III) with the compound of formula (IV) in the presence of a halogenating agent. In other processes, the compound of the formula (I) is produced by reacting a mixed acid anhydride, which is prepared by reacting the compound of formula (III) with isobutyl chloroformate, with the compound of formula (IV) at low temperature of --20.degree. C. to --10.degree. C. under anhydrous condition.
However, the former prior art methods have many deficiencies since the use of a large amount of a hazardous halogenating agent and a laborious distillation process are required. Furthermore, in the latter prior art methods, there is instability in the use of the mixed acid anhydride so that it is difficult to mass produce the compound of formula (I).